EP1243260A1 - Cicatrizant hydrocolloidal patch containing hyaluronic acid and chondroitin sulphate - Google Patents
Cicatrizant hydrocolloidal patch containing hyaluronic acid and chondroitin sulphate Download PDFInfo
- Publication number
- EP1243260A1 EP1243260A1 EP02006344A EP02006344A EP1243260A1 EP 1243260 A1 EP1243260 A1 EP 1243260A1 EP 02006344 A EP02006344 A EP 02006344A EP 02006344 A EP02006344 A EP 02006344A EP 1243260 A1 EP1243260 A1 EP 1243260A1
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- Prior art keywords
- patch
- weight
- adhesive layer
- total weight
- layer
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/58—Adhesives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/225—Mixtures of macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
Definitions
- the present invention concerns a cicatrizant hydrocolloidal patch and the relative preparation process.
- Cicatrizant pharmaceutical formulations for topical use based on hyaluronic acid or a pharmaceutical salt thereof, have been known for some time.
- EP 0480198 describes pharmaceutical compositions containing the sodium salt of hyaluronic acid and antiseptic substances for topical use.
- compositions are in hydrogel form and have the disadvantage of adding liquid to the wound when applied to it, hence making it even more difficult to eliminate the exudate from the wound.
- This film is prepared with a process that envisages the following steps:
- a cicatrizant hydrocolloidal patch comprising a support layer, an intermediate layer containing an adhesive polymer, at least one hydrocolloid and hyaluronic acid or a pharmaceutical salt thereof and, finally, a protective layer.
- This patch does not show sufficient cicatrizant strength even at concentrations of hyaluronic acid in the order of 2% in weight out of the weight of the adhesive layer. In fact, the cicatrizant effect does not diverge, in a statistically significant manner, from the cicatrizant activity shown by the placebo patch, not containing any active principle.
- the Applicant has now unexpectedly discovered a cicatrizant hydrocolloidal patch containing hyaluronic acid and chondroitin sulphate as the active principle which, even at low concentrations of both chondroitin sulphate and hyaluronic acid, when it is applied to a wound allows to attain a cicatrization speed, expressed as percentage of reduction of the wound surface in time, comparable to that of bandages available on the market for the same purposes, namely CONVATEC® or VARIHESIVE-E®, but, unlike the latter, also promotes the formation of dermis and collagen production.
- the object of the present invention is therefore a cicatrizant hydrocolloidal patch comprising:
- the patch object of the present invention preferably contains hyaluronic acid in the form of one of its pharmaceutically acceptable salts at concentrations preferably between 0.01 and 5%, in weight out of the total weight of adhesive layer (b).
- the molecular weight of the hyaluronic acid is preferably between 50,000 and 1,000,000.
- the chondroitin sulphate in the patch of the present invention is preferably the bisodium salt of chondroitin-4-sulphate or chondroitin sulphate A, and the concentration of said active principle is preferably between 0.01% in weight and 5%.
- the aforesaid salt will hereafter be defined by the term sodium chondroitin sulphate.
- the concentration of sodium hyaluronate in the patch according to the present invention is between 0.05 and 1%, and that of sodium chondroitin sulphate is between 0.05 and 1%.
- the patch of the invention shows a greater cicatrizant effect compared to that a patch of similar formulation, but containing sodium hyaluronate at a concentration of 2% and sodium chondroitin sulphate at a concentration of 3% in weight out of the total weight of the adhesive layer, and comparable to that of bandages available on the market such as VARIHESIVE®.
- Preferred hydrocolloids for use in adhesive layer (b) of the patch according to the present invention are sodium carboxymethylcellulose of molecular weight of between 700 and 50,000, pectin USPL optionally mixed with saccharose, or mixtures thereof.
- the concentration of said hydrocolloid is preferably between 10 and 90% in weight out of the total weight of adhesive layer (b).
- a mixture of the following is used as a hydrocolloid: sodium carboxymethylcellulose, commercially available under the trade name of Blancosa® 7H4XF, sodium carboxymethylcellulose commercially available under the trade name of CEKOL®, Pectin USPL available under the trade name of GENU-PECTIN, added with saccharose (Sugar mix).
- This mixture of hydrocolloids is preferably present in adhesive layer (b) at concentrations of between 10 and 80%, even more preferably at concentrations of 47% in weight out of the total weight of said adhesive layer (b).
- the adhesive polymer of layer (b) of the patch object of the present invention is preferably chosen between polyisobutylene of molecular weight of between 500 and 100,000, isoprene/styrene copolymer or mixtures thereof, at concentrations of between 10 and 90% in weight out of the total weight of adhesive layer (b).
- a mixture of polyisobutylene having a mean molecular weight of 40,000 and commercially available under the trade name of Oppanol® B15, and of styrene/isoprene copolymer Kraton® D-1107CS is used.
- the concentration of said adhesive polymeric mixture in layer (b) is preferably between 10 and 80%, even more preferably of 45% in weight out of the total weight of the adhesive layer (b).
- the patch according to the present invention preferably contains a plasticizer chosen in the group consisting of mineral oil optionally with traces of white naphthenic oil, commercially available under the trade name of ENERPAR® and a mixture of polyterpenic resin and petroleum hydrocarbon resin, commercially available under the trade name of WINGTAC®10, and relative mixtures of said plasticizers at concentrations of between 0.5 and 25% in weight calculated out of the total weight of said adhesive layer (b).
- a plasticizer chosen in the group consisting of mineral oil optionally with traces of white naphthenic oil, commercially available under the trade name of ENERPAR® and a mixture of polyterpenic resin and petroleum hydrocarbon resin, commercially available under the trade name of WINGTAC®10, and relative mixtures of said plasticizers at concentrations of between 0.5 and 25% in weight calculated out of the total weight of said adhesive layer (b).
- a plasticizer chosen in the group consisting of mineral oil optionally with traces of white naphthenic oil, commercially available under the trade name of
- the support or layer (a) is made up of polyurethane as a film or a foam, while layer (c), which is the sheet removable at the moment of use, is preferably made of silicon paper.
- the patch object of the present invention is preferably produced with a process that comprises the following steps:
- composition of the hydrocolloidal patch according to the present invention Shown below are two illustrative but non-limiting examples of composition of the hydrocolloidal patch according to the present invention.
- Hydrocolloidal patch composed of:
- each patch was sealed in a special airtight blister pack and irradiated with ⁇ rays (normally between 25 and 50 KGy)
- a rectangular wound of 12 cm 2 (4x3) was made on one side of each guinea pig (10 guinea pigs + 1 extra per group), maintaining the panniculus carnosus.
- the medication was applied to the wound each day up to day 33 (end of the experiment).
- the action of the medication and the appearance of the wounds were macroscopically analyzed following a scale of criteria based on moisture, adherence to the wound, inflammatory and haemorrhagic process and level of cicatrization.
- a photograph was taken every two or three removals of the medication under standard conditions in order to automatically highlight the progress of the surface of the wound with an image analyser.
- the speed in cicatrization is better in groups B and D.
- the experiment was stopped at day 33 and the skin of three animals was taken for each group. After fixing with 10% formaldehyde, the samples were then denatured in alcohol solutions of increasing concentration and afterwards incorporated in paraffin.
- the pairs of histological samples were observed using a Polyvar microscope (Reichert) fitted with a 4, 10 and 25 objective with the possibility of adding a 1.25 lens.
- Hypervascularization and exudates consisting of red blood cells and the presence of a foamy collagen-based matrix in the deep layers of the granulation tissue, were found in both groups. However, group A was associated with a more marked hypervascularization and inflammatory component when compared to group D.
- the wounds of groups B and C show similar characteristics with respect to those of groups A and D, but, in addition, in the former ones the presence of a more mature deep dermis is observed.
- the collagen is denser and very similar to the adjacent layer of the normal dermis. This is particularly marked for the wounds of group C.
- this group also shows a relative superficial granulation tissue of inflammatory type with a weakening of the epidermization process when compared to the wounds of group B.
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- Health & Medical Sciences (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
- The present invention concerns a cicatrizant hydrocolloidal patch and the relative preparation process.
- Cicatrizant pharmaceutical formulations for topical use, based on hyaluronic acid or a pharmaceutical salt thereof, have been known for some time.
- For instance EP 0480198 describes pharmaceutical compositions containing the sodium salt of hyaluronic acid and antiseptic substances for topical use.
- However, these compositions are in hydrogel form and have the disadvantage of adding liquid to the wound when applied to it, hence making it even more difficult to eliminate the exudate from the wound.
- These drawbacks are solved with the self-supporting dry transparent film described in international patent application WO 97/02845, consisting of a mixture of at least one hydrocolloid and hyaluronic acid.
- This film is prepared with a process that envisages the following steps:
- preparation of a very diluted aqueous composition containing hyaluronic acid at concentrations between 0.5 and 2% in weight, and hydrocolloids at concentrations between 1% and 20% optionally in the presence of an additional solvent such as glycerol.
- · casting of the composition on a support,
- · exsiccation of all the liquid components of the aforesaid composition by treatment in a stove.
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- An anhydrous film is thus obtained in which the content of hyaluronic acid is between 2 and 98% and the remaining components to 100% are the hydrocolloids. The complete elimination of the water, achieved by exsiccation in a stove requires extremely long heating times (in the order of several hours), with a consequent notable waste of energy. In addition, since with this type of procedure it is difficult to obtain a film of uniform thickness with a constant level of anhydricity, the industrial implementation of such a process is virtually impracticable.
- Moreover, all the hydrocolloids, with the exclusion of polyvinylpyrrolidone, tend to worsen the mechanical properties of the self-supporting film, namely its tensile strength and elongation at break. To obviate such a drawback large quantities of the expensive hyaluronic acid must be added, in most cases, more than 10% and, in some cases, in the event that sodium alginate is used as the hydrocolloid, in amounts decidedly greater than 25%. Only when polyvinylpyrrolidone is employed it is possible to obtain good mechanical properties using smaller amounts of hyaluronic acid, which in any case must be around 2.5%.
- In Italian patent 1301470 a cicatrizant hydrocolloidal patch is described comprising a support layer, an intermediate layer containing an adhesive polymer, at least one hydrocolloid and hyaluronic acid or a pharmaceutical salt thereof and, finally, a protective layer.
- This patch does not show sufficient cicatrizant strength even at concentrations of hyaluronic acid in the order of 2% in weight out of the weight of the adhesive layer. In fact, the cicatrizant effect does not diverge, in a statistically significant manner, from the cicatrizant activity shown by the placebo patch, not containing any active principle.
- In "Effect of chondroitin sulfate preparation on wound healing and strength of the surgical scar" by M. Fialkova et al BYULLETTIN EKSPERIMENTAL' NOY BIOLOGII I MEDITSINY, Vol. 108, N°9 pp. 350-351 the results of an experiment carried out on a model of "full thickness" (300 mm2) cutaneous wound in rats are discussed, wherein such a wound has been treated with one or two applications of 30 mg of sodium chondroitin sulphate. The reduction of the damaged surface (measuring through planimetry) was more rapid in the treated group. For instance, 8 days after the second application the residual area in the treated group was half that of the control group, and also the clinical signs connected with the lesion (edema-exudate) decreased more quickly in the treated group.
- The therapeutic form considered in this article diverges from that considered in the Italian patent since the active principle is administered intramuscularly by means of an injectable solution and at high concentrations of 10%.
- The Applicant has now unexpectedly discovered a cicatrizant hydrocolloidal patch containing hyaluronic acid and chondroitin sulphate as the active principle which, even at low concentrations of both chondroitin sulphate and hyaluronic acid, when it is applied to a wound allows to attain a cicatrization speed, expressed as percentage of reduction of the wound surface in time, comparable to that of bandages available on the market for the same purposes, namely CONVATEC® or VARIHESIVE-E®, but, unlike the latter, also promotes the formation of dermis and collagen production.
- The object of the present invention is therefore a cicatrizant hydrocolloidal patch comprising:
- a) a support layer,
- b) an adhesive layer containing an adhesive polymer, at least one hydrocolloid, hyaluronic acid or a phrmaceutical salt thereof and chondroitin sulphate or a pharmaceutical salt thereof,
- c) a protective layer removable at the moment of use.
-
- The patch object of the present invention preferably contains hyaluronic acid in the form of one of its pharmaceutically acceptable salts at concentrations preferably between 0.01 and 5%, in weight out of the total weight of adhesive layer (b).
- The molecular weight of the hyaluronic acid is preferably between 50,000 and 1,000,000.
- The chondroitin sulphate in the patch of the present invention is preferably the bisodium salt of chondroitin-4-sulphate or chondroitin sulphate A, and the concentration of said active principle is preferably between 0.01% in weight and 5%. For simplification the aforesaid salt will hereafter be defined by the term sodium chondroitin sulphate.
- According to a particularly preferred solution, the concentration of sodium hyaluronate in the patch according to the present invention is between 0.05 and 1%, and that of sodium chondroitin sulphate is between 0.05 and 1%.
- In fact, it has surprisingly been found that, when such active principles have concentrations that fall within the aforesaid preferred intervals and particularly when sodium hyaluronate has a concentration of 0.2% and sodium chondroitin sulphate has a concentration of 0.3% in weight out of the total weight of adhesive layer (b), the patch of the invention shows a greater cicatrizant effect compared to that a patch of similar formulation, but containing sodium hyaluronate at a concentration of 2% and sodium chondroitin sulphate at a concentration of 3% in weight out of the total weight of the adhesive layer, and comparable to that of bandages available on the market such as VARIHESIVE®.
- Preferred hydrocolloids for use in adhesive layer (b) of the patch according to the present invention are sodium carboxymethylcellulose of molecular weight of between 700 and 50,000, pectin USPL optionally mixed with saccharose, or mixtures thereof.
- The concentration of said hydrocolloid is preferably between 10 and 90% in weight out of the total weight of adhesive layer (b).
- According to a particularly preferred solution, a mixture of the following is used as a hydrocolloid: sodium carboxymethylcellulose, commercially available under the trade name of Blancosa® 7H4XF, sodium carboxymethylcellulose commercially available under the trade name of CEKOL®, Pectin USPL available under the trade name of GENU-PECTIN, added with saccharose (Sugar mix). This mixture of hydrocolloids is preferably present in adhesive layer (b) at concentrations of between 10 and 80%, even more preferably at concentrations of 47% in weight out of the total weight of said adhesive layer (b).
- The adhesive polymer of layer (b) of the patch object of the present invention is preferably chosen between polyisobutylene of molecular weight of between 500 and 100,000, isoprene/styrene copolymer or mixtures thereof, at concentrations of between 10 and 90% in weight out of the total weight of adhesive layer (b).
- According to a particularly preferred solution a mixture of polyisobutylene having a mean molecular weight of 40,000 and commercially available under the trade name of Oppanol® B15, and of styrene/isoprene copolymer Kraton® D-1107CS is used. The concentration of said adhesive polymeric mixture in layer (b) is preferably between 10 and 80%, even more preferably of 45% in weight out of the total weight of the adhesive layer (b).
- The patch according to the present invention preferably contains a plasticizer chosen in the group consisting of mineral oil optionally with traces of white naphthenic oil, commercially available under the trade name of ENERPAR® and a mixture of polyterpenic resin and petroleum hydrocarbon resin, commercially available under the trade name of WINGTAC®10, and relative mixtures of said plasticizers at concentrations of between 0.5 and 25% in weight calculated out of the total weight of said adhesive layer (b). According to a preferred solution a mixture of the aforesaid mineral oil and of the mixture of polyterpenic resin/petroleum hydrocarbon resin is used and the total concentration of said plasticizer is between 1 and 10%, and even more preferably of 8% in weight out of the total weight of the adhesive layer (b).
- In the patch according to the present invention preferably the support or layer (a) is made up of polyurethane as a film or a foam, while layer (c), which is the sheet removable at the moment of use, is preferably made of silicon paper.
- The patch object of the present invention is preferably produced with a process that comprises the following steps:
- i) dry mixing of hyaluronic acid or a pharmaceutical salt thereof and chondroitin sulphate or a pharmaceutical salt thereof with the hydrocolloid,
- ii) mixing of the powders of the previous stage with the adhesive composition and optionally a plasticizer;
- iii) extrusion of the paste deriving from step (ii) at a temperature of between 40 and 90°C, preferably of 80°C, between the support layer (a) and the removable protective layer (c).
-
- Shown below are two illustrative but non-limiting examples of composition of the hydrocolloidal patch according to the present invention.
-
- 1. layer (c): silicon paper = 0.82 g/total weight of the patch
- 2. layer (b): adhesive = 10.25g/total weight of the patch,
- 3. layer (a): polyurethane support film = 0.62 g/total weight of the patch.
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Trade name Usual name % in weight out of the total weight of layer (b) OPPANOL® B15 Polyisobutylene 29.24 KRATON®D-1107CS Styrene-isoprene copolymer 15.59 BLANCOSA® 7H4XF Sodium carboxymethylcellulose 17.55 GENU-PECTIN Pectin USPL 11.70 CEKOL®4000 Sodium carboxymethylcellulose 15.59 SUGARMIX® Saccharose 1.95 WINGTAC®10 Synthetic polyterpenic resin/ petroleum hydrocarbon resin 3.90 ENERPAR® Mineral oil with traces of white naphthenic oil 3.90 Sodium hyaluronate 0.23 Sodium chondroitin sulphate 0.35 -
Trade name Usual name % in weight out of the total weight of layer (b) OPPANOL® B15 Polyisobutylene 27.78 KRATON®D-1107CS Styrene-isoprene copolymer 14.82 BLANCOSA ® 7H4XF Sodium carboxymethylcellulose 16.67 GENU-PECTIN Pectin USPL 11.11 CEKOL®4000 Sodium carboxymethylcellulose 14.82 SUGARMIX® Saccharose 1.85 WINGTAC®10 Synthetic polyterpenic resin/ petroleum hydrocarbon resin 3.70 ENERPAR® Mineral oil with traces of white naphthenic oil 3.70 Sodium hyaluronate 2.22 Sodium chondroitin sulphate 3.33 - After cutting, each patch was sealed in a special airtight blister pack and irradiated with γrays (normally between 25 and 50 KGy)
- Dunkin Hartley type guinea pigs were used for this test.
- A rectangular wound of 12 cm2 (4x3) was made on one side of each guinea pig (10 guinea pigs + 1 extra per group), maintaining the panniculus carnosus.
- The medication was applied to the wound each day up to day 33 (end of the experiment).
- The action of the medication and the appearance of the wounds were macroscopically analyzed following a scale of criteria based on moisture, adherence to the wound, inflammatory and haemorrhagic process and level of cicatrization.
- A photograph was taken every two or three removals of the medication under standard conditions in order to automatically highlight the progress of the surface of the wound with an image analyser.
- The following types of medication were tested.
- group A: placebo hydrocolloidal patch
- group B: hydrocolloidal plasters of example 1
- group C: hydrocolloidal plaster of example 2
- group D: VARIHESIVE ® patch
- The wounds of groups A, B, and C were moist, dark and sanguinolent for most of the time, whereas the wounds of group D were moist but not as dark as those in the other groups and also less sanguinolent. However, in the latter case some yellow liquid was observed in the wounds after day 5.
- A certain tendency towards better cicatrization was observed in group B when compared to group A. In fact, the wounds in group B were smaller and had a better macroscopic aspect, since covered by a thinner scab.
-
evolution of the mean surface of the wound in different groups (cm2) Day GROUP A GROUP B GROUP C GROUP D 1 13.60 13.89 13.41 12.83 5 10.26 9.58 9.59 8.87 7 9.88 8.27 9.34 6.76 11 6.73 5.45 5.41 4.92 15 5.01 3.99 4.57 3.74 19 4.27 3.21 3.82 3.10 24 3.17 2.54 3.15 2.37 28 2.87 2.30 2.82 2.32 31 2.54 1.83 2.49 2.33 33 2.48 1.72 2.38 1.72 - The results reported above show that in all groups the surface of the wound was reduced of approximately 50% in the first 11 days and was reduced more slowly afterwards.
- A difference in the speed of cicatrization is observed between the different groups:
- 50% cicatrization of the surface for groups B and D at 8.3 and 8 days respectively, while in groups A and C this cicatrization is obtained at 10.9 and 9.4 days respectively.
- 75% cicatrization of the surface of the skin for groups B and D at 18.6 and 18.9 days respectively, while for groups A and C this value is reached at 23.8 and 23.7days respectively.
- The speed in cicatrization is better in groups B and D.
- Statistical analysis of the residual surface (non-parametric Mann & Whitney test) did not show any significant difference (p< 0.05) between groups B and D, while cicatrization in groups A and C showed the same course.
- The experiment was stopped at day 33 and the skin of three animals was taken for each group. After fixing with 10% formaldehyde, the samples were then denatured in alcohol solutions of increasing concentration and afterwards incorporated in paraffin.
- Two pairs in a series, of approx. 5 µm thickness, were made on each sample with the aid of a HM350 microtome. The sections were dyed according to a modified trichromium technique for classic histopathological analysis and with toluidine blue to highlight metachromatic oxydic structures.
- The pairs of histological samples were observed using a Polyvar microscope (Reichert) fitted with a 4, 10 and 25 objective with the possibility of adding a 1.25 lens.
- The wounds of the animals of group A and group D give similar results from a histological point of view.
- Hypervascularization and exudates consisting of red blood cells and the presence of a foamy collagen-based matrix in the deep layers of the granulation tissue, were found in both groups. However, group A was associated with a more marked hypervascularization and inflammatory component when compared to group D.
- The wounds of groups B and C show similar characteristics with respect to those of groups A and D, but, in addition, in the former ones the presence of a more mature deep dermis is observed. The collagen is denser and very similar to the adjacent layer of the normal dermis. This is particularly marked for the wounds of group C.
- However, this group also shows a relative superficial granulation tissue of inflammatory type with a weakening of the epidermization process when compared to the wounds of group B.
- Therefore, the active principles of the patches applied to groups B and C show a twoford effect, that is:
- 1) improved synthesis of collagen and organization in the deep layers of the wounds of groups (B) and in particular (C),
- 2) a more marked superficial inflammatory component associated with these active principles in the case of the groups (C).
-
Claims (21)
- Cicatrizant hydrocolloidal patch comprisinga) a support layer,b) an adhesive layer containing an adhesive polymer, at least one hydrocolloid, hyaluronic acid or a pharmaceutical salt thereof, chondroitin sulphate or a pharmaceutical salt thereof,c) a protective layer removable at the moment of use.
- The patch as in claim 1, characterized in that it contains hyaluronic acid in the form of one of its pharmaceutically acceptable salts at concentrations of between 0.01 and 5% in weight out of the total weight of adhesive layer (b).
- The patch as in claim 2, characterized in that it uses the sodium salt of hyaluronic acid at concentrations of between 0.05% and 1% in weight out of the total weight of adhesive layer (b).
- The patch as in any one of claims 1-3, characterized in that the molecular weight of hyaluronic acid is preferably between 50,000 and 1,000,000.
- The patch as in any one of claims 1-4, characterized in that the chondroitin sulphate in the patch is sodium chondroitin sulphate, and the concentration of said active principle is between 0.01% in weight and 5% in weight out of the total weight of adhesive layer (b).
- The patch as in claims 3 or 5, characterized in that the concentration of the sodium hyaluronate is between 0.05 and 1% and that of sodium chondroitin sulphate is between 0.05 and 1% in weight out of the total weight of adhesive layer (b).
- The plaster as in claim 6, characterized in that the concentration of sodium hyaluronate is 0.2% and that of sodium chondroitin sulphate is 0.3% out of the total weight of adhesive layer (b).
- The patch as in any one of claims 1-7, characterized in that the hydrocolloid is chosen from the group consisting of sodium carboxymethylcellulose of molecular weight of between 700 and 50,000, pectin USPL optionally mixed with saccharose, or relative mixtures thereof.
- The patch as in claim 8, characterized in that the concentration of said hydrocolloid is between 10 and 90% in weight out of the total weight of adhesive layer (b).
- The patch as in any one of claims 8 and 9, characterized in that said hydrocolloid is a mixture of sodium carboxymethylcellulose and pectin USPL added with saccharose at concentrations of between 10 and 80% in weight out of the total weight of adhesive layer (b).
- The patch as in claim 10, in which the concentration of said hydrocolloid is equal to 47% in weight.
- The patch as in any one of claims 1-11, characterized in that the adhesive polymer of layer (b) is chosen between polyisobutylene of molecular weight of between 500 and 100,000, isoprene/styrene copolymer, or relative mixtures thereof, at concentrations of between 10 and 90% in weight out of the total weight of adhesive layer (b).
- The patch as in claim 12, characterized in that the adhesive polymer of layer (b) consists of a mixture of polyisobutylene with a molecular weight of 40,000 and of styrene/isoprene copolymer at a concentration of between 10 and 80% in weight out of the total weight of adhesive layer (b).
- The patch as in claim 13, characterized in that the concentration of said polymeric mixture is equal to 45% in weight out of the total weight of adhesive layer (b).
- The patch as in any one of claims 1-14, characterized in that it contains a plasticizer chosen from the group consisting of mineral oil optionally with traces of white naphthenic oil, a mixture of petroleum hydrocarbon resin and polyterpenic resin, and relative mixtures of said plasticizers at concentrations of between 0.5 and 25% in weight calculated out of the total weight of said adhesive layer (b).
- The patch as in claim 15, characterized in that said plasticizer is a mixture of said mineral with said mixture of polyterpenic resin/ petroleum hydrocarbon resin and the total concentration of said plasticizer is between 1 and 10% in weight out of the total weight of adhesive layer (b).
- The patch as in claim 16, characterized in that the concentration of said plasticizer is approx. 8% in weight out of the total weight of adhesive layer (b).
- The patch as in any one of claims 1-17, characterized in that the support layer (a) consists of polyurethane as a film or foam.
- The patch as in any one of claims 1-18, characterized in that layer (c), the sheet removable at the moment of use, is preferably made of silicon paper.
- Process to prepare the patch as in any one of claims 1-19 comprising the following steps:i) dry mixing of the hyaluronic acid and chondroitin sulphate with the hydrocolloid,ii) mixing of the powders of the previous stage with the adhesive composition and optionally a plasticizer;iii) extrusion of the paste deriving from step (ii) at a temperature of between 40 and 90°C between support layer (a) and the removable protective layer (c).
- The process as in claim 20, characterized in that the temperature of stage (iii) is 80°C.
Priority Applications (1)
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DK02006344T DK1243260T3 (en) | 2001-03-22 | 2002-03-21 | Formation-promoting hydrocolloid patch containing hyaluronic acid and chondroitin sulfate |
Applications Claiming Priority (2)
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ITMI010611 | 2001-03-22 | ||
IT2001MI000611A ITMI20010611A1 (en) | 2001-03-22 | 2001-03-22 | CICATRIZING HYDROCOLLOIDAL PATCH CONTAIN HYALURONIC ACID AND CHONDROITIN SULPHATE |
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EP1243260A1 true EP1243260A1 (en) | 2002-09-25 |
EP1243260B1 EP1243260B1 (en) | 2005-06-15 |
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EP02006344A Expired - Lifetime EP1243260B1 (en) | 2001-03-22 | 2002-03-21 | Cicatrizant hydrocolloidal patch containing hyaluronic acid and chondroitin sulphate |
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US (1) | US20030124175A1 (en) |
EP (1) | EP1243260B1 (en) |
AT (1) | ATE297718T1 (en) |
CA (1) | CA2378038A1 (en) |
DE (1) | DE60204614T2 (en) |
DK (1) | DK1243260T3 (en) |
ES (1) | ES2244689T3 (en) |
IT (1) | ITMI20010611A1 (en) |
PT (1) | PT1243260E (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009138843A1 (en) * | 2008-05-13 | 2009-11-19 | Hertek S.A. | Glycosaminoglycan oral use and compositions |
US9241953B2 (en) | 2008-05-13 | 2016-01-26 | Apharm S.R.L. | Glycosaminoglycan oral use and compositions |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8467868B1 (en) * | 2005-04-26 | 2013-06-18 | University Of South Florida | Method of transdermal drug delivery |
Citations (2)
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EP0302536A1 (en) * | 1982-04-22 | 1989-02-08 | E.R. Squibb & Sons, Inc. | Granules for use in treating wounds |
DE19712699A1 (en) * | 1997-03-26 | 1998-10-01 | Thueringisches Inst Textil | Rapid dressing for wounds, used to improve environment of wound |
Family Cites Families (6)
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IT1212892B (en) * | 1983-10-11 | 1989-11-30 | Della Valle Francesco | HYALURONIC ACID OBTAINED BY MEANS OF MOLECULAR FILTRATION WITHOUT INFLAMMATORY ACTIVITY AND ITS THERAPEUTIC USE |
SE9101853D0 (en) * | 1991-06-17 | 1991-06-17 | Jonas Wadstroem | IMPROVED TISSUE ASHESIVE |
DE4416927C1 (en) * | 1994-05-13 | 1995-08-31 | Lohmann Therapie Syst Lts | Device for release of active agents from melt-type adhesive |
US6309661B1 (en) * | 1996-02-28 | 2001-10-30 | Carla A. Haynes | Solid polysaccharide materials for use as wound dressings |
US5928174A (en) * | 1997-11-14 | 1999-07-27 | Acrymed | Wound dressing device |
US20020025921A1 (en) * | 1999-07-26 | 2002-02-28 | Petito George D. | Composition and method for growing, protecting, and healing tissues and cells |
-
2001
- 2001-03-22 IT IT2001MI000611A patent/ITMI20010611A1/en unknown
-
2002
- 2002-03-21 ES ES02006344T patent/ES2244689T3/en not_active Expired - Lifetime
- 2002-03-21 PT PT02006344T patent/PT1243260E/en unknown
- 2002-03-21 AT AT02006344T patent/ATE297718T1/en not_active IP Right Cessation
- 2002-03-21 CA CA002378038A patent/CA2378038A1/en not_active Abandoned
- 2002-03-21 US US10/104,410 patent/US20030124175A1/en not_active Abandoned
- 2002-03-21 DE DE60204614T patent/DE60204614T2/en not_active Expired - Fee Related
- 2002-03-21 DK DK02006344T patent/DK1243260T3/en active
- 2002-03-21 EP EP02006344A patent/EP1243260B1/en not_active Expired - Lifetime
Patent Citations (2)
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EP0302536A1 (en) * | 1982-04-22 | 1989-02-08 | E.R. Squibb & Sons, Inc. | Granules for use in treating wounds |
DE19712699A1 (en) * | 1997-03-26 | 1998-10-01 | Thueringisches Inst Textil | Rapid dressing for wounds, used to improve environment of wound |
Non-Patent Citations (4)
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BIULLETEN' EKSPERIMENTAL'NOI BIOLOGII I MEDITSINY. USSR SEP 1989, vol. 108, no. 9, September 1989 (1989-09-01), pages 350 - 351, ISSN: 0365-9615 * |
CHEN W Y ET AL: "Functions of hyaluronan in wound repair.", WOUND REPAIR AND REGENERATION: OFFICIAL PUBLICATION OF THE WOUND HEALING SOCIETY [AND] THE EUROPEAN TISSUE REPAIR SOCIETY. UNITED STATES 1999 MAR-APR, vol. 7, no. 2, March 1999 (1999-03-01), pages 79 - 89, XP002202621, ISSN: 1067-1927 * |
DATABASE MEDLINE [online] September 1989 (1989-09-01), FIALKOVA M A ET AL: "[The effect of chondroitin sulfate preparations on wound healing and the strength of the surgical scar]", XP002202622, Database accession no. NLM2514813 * |
SUYAMA T ET AL: "The acceleration of wound healing with chondroitin sulfate A and its acidic hydrolysates.", THE JAPANESE JOURNAL OF EXPERIMENTAL MEDICINE. JAPAN AUG 1966, vol. 36, no. 4, August 1966 (1966-08-01), pages 449 - 452, XP002202620, ISSN: 0021-5031 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009138843A1 (en) * | 2008-05-13 | 2009-11-19 | Hertek S.A. | Glycosaminoglycan oral use and compositions |
EA018333B1 (en) * | 2008-05-13 | 2013-07-30 | Афарм С.Р.Л. | Glycosaminoglycan oral use and compositions |
US8735373B2 (en) | 2008-05-13 | 2014-05-27 | Apharm S.R.L. | Glycosaminoglycan oral use and compositions |
US9241953B2 (en) | 2008-05-13 | 2016-01-26 | Apharm S.R.L. | Glycosaminoglycan oral use and compositions |
Also Published As
Publication number | Publication date |
---|---|
DE60204614D1 (en) | 2005-07-21 |
ATE297718T1 (en) | 2005-07-15 |
ES2244689T3 (en) | 2005-12-16 |
ITMI20010611A1 (en) | 2002-09-22 |
DK1243260T3 (en) | 2005-09-05 |
CA2378038A1 (en) | 2002-09-22 |
US20030124175A1 (en) | 2003-07-03 |
DE60204614T2 (en) | 2006-05-11 |
EP1243260B1 (en) | 2005-06-15 |
ITMI20010611A0 (en) | 2001-03-22 |
PT1243260E (en) | 2005-10-31 |
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